DESCRIPTION: (Adapted from the abstract) Blood pressure and cardiac function are importantly regulated by arterial baroreflexes, yet the cellular basis of these reflexes is uncertain. The long-term goal of this research is to understand how the central nervous system (CNS) portion of these reflexes works under normal and pathophysiological conditions such as hypertension, cardiac arrhythmia and heart failure. The nucleus tractus solitarius (NTS) is the location of the first CNS neurons involved in baroreflex function. The present proposal is designed to examine fundamental cellular mechanisms at work in NTS neurons: basic discharge characteristics, connections, communication, and interactions. A rat medullary brainslice will be used with intracellular recordings to study neurons in an area densely innervated by aortic baroreceptor (BR) synapses. This preparation allows to very selectively activate sensory axons in the solitary tract (ST) and examine responses at the first stage of sensory information processing. BRs can be selectively labeled in the rat offering direct anatomical evidence of cardiovascular innervation in the neurons studied. The major goal of this work is to test the hypothesis that NTS is the site of a major transformation of sensory information and that this process importantly shapes the performance characteristics of the overall baroreflex control of the circulation. The studies are focussed on understanding the basic mechanisms which underlie the processing and transfer of sensory information by NTS. Both the pre- and postsynaptic elements of the sensory afferent (ST-NTS) synapse will be examined as well as the intrinsic properties of NTS neurons. The principal investigator's current attention is on the following key areas: frequency dependent synaptic depression, presynaptic targets for modulation (particularly calcium channel subtypes), excitatory amino acid receptor interactions, and the character of local circuit interactions within NTS. Specific Aims concern modulation of ST-NTS synaptic transmission by preferential actions of peptides on presynaptic calcium channel subtypes, presynaptic GABAB receptors, frequency dependent sensory synaptic depression, differential NMDA sensitivity, the role of metabotropic receptors and glutamate reuptake in synaptic responses, comparison of horizontal and transverse slices of NTS, and non-glutamatergic neurotransmitters. Together, these aims will provide new and direct information about the CNS mechanisms of integration and information processing at first stage of cardiovascular regulation and the autonomic control of the heart and blood vessels.